Prostate Cancer Androgen Deprivation and Chemo: Does Timing Matter?

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Earlier androgen deprivation therapy may increase death risk, but earlier docetaxel may lower it.
Earlier androgen deprivation therapy may increase death risk, but earlier docetaxel may lower it.

Recent reports may help to inform clinical decision-making with respect to the timing of androgen deprivation therapy (ADT) and chemotherapy in patients with recurrent or advanced prostate cancer (PCa).

According to results of a study led by Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, CA, early ADT may increase the risk of death among men who receive it after experiencing biochemical recurrence (BCR) of PCa following radical prostatectomy.1

This adverse effect appears to be limited to men younger than 65 when they experience BCR and those with low-risk disease.

The study retrospectively analyzed data from 468 patients who experienced BCR after radical prostatectomy. The median follow-up after BCR was 70 months. Of the 135 men who received early ADT (defined as receipt of ADT when prostate-specific antigen [PSA] levels were less than 5 ng/mL), 42 died.

In adjusted analyses, early ADT was associated with a 68% increased risk of death compared with the 333 men who received conventional therapy (no ADT or ADT started when PSA levels were 5 ng/mL or higher).

When the researchers stratified the men by age, early ADT was associated with a 5.6 times increased risk of death compared with conventional therapy among men younger than 65, and a 61% decreased risk among those 65 and older. Early ADT was associated with a 3.2 times increased mortality in patients with low-risk disease, but did not significantly affect survival in those with high-risk disease.

Finally, the data suggest that men with a PSA doubling time of less than 9 months fared better with early ADT, whereas those with longer PSA doubling times fared worse. While presenting their research at the American Urological Association (AUA) 2015 annual meeting in New Orleans, LA, Dr. Freedland's team concluded that the “risks and benefits of ADT must be weighed and taken into account when deciding timing of treatment.”

Whether the harmful effect of early ADT is due to true harm, treatment bias, or unmeasured confounding factors is not known, they noted.

“These data support other recent data that ADT can come with a price, and is not appropriate for all men. It should be used selectively for those men at the highest risk of death from prostate cancer,” Dr. Freedland said in an interview with Cancer Therapy Advisor.

Salvage ADT

In a separate study presented at the AUA 2015 annual meeting, researchers found that delaying salvage ADT in patients with PCa who experience BCR after brachytherapy did not adversely impact all-cause or cancer-specific survival.2

A total of 115 men who received brachytherapy and experienced biochemical failure according to the Phoenix definition were included. The investigators stratified patients by receipt of immediate or delayed ADT and by receipt of ADT at a PSA threshold of 10 ng/mL. Forty men had immediate ADT and 75 had delayed ADT (3 or more months after recurrence was identified).

RELATED: HOXB13 G84E Mutation Associated with Risk of Prostate Cancer

During a median follow-up of 11.5 years, 56 patients died, 37 from PCa. Patients receiving immediate ADT had higher PSA levels at failure than the delayed ADT group (11.6 vs. 5.6 ng/mL).

The median delay to salvage ADT was 1.8 years. Delayed ADT and a PSA threshold of 10 were not significantly associated with all-cause or cancer-specific mortality.

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